In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
Abstract:
Introduction: A gender gap exists in stroke, with increased morbidity and mortality in women. The underlying mechanisms remain unknown, although differences in platelet biology may play a role. Inhibition of the interaction between VWF and GP 1B-IX-V has demonstrated thrombolytic efficacy. Hypothesis: We hypothesized that sex differences in reperfusion after stroke were attributable to the VWF-GP IB-IX-V axis, and inhibition of this interaction would yield clear discrepancies. Methods: Adult wild-type (C57BL/6J) mice were anesthetized, the right carotid artery exposed and baseline carotid flow obtained by Doppler. Thrombosis was induced with a FeCl 3 patch. After 20-minute stabilization, mice were intravenously administered vehicle (n, male=12, female=8) or VWF aptamer. Aptamer (0.5 mg/kg) administration was assessed using a bolus (5 min; n, male=5, female=8) method. Given the minimal observed thrombolytic effect in females, a continuous infusion (45 min; n, female=5) was also attempted. Next, blood from male (n=8) and female (n=8) adult wild-type beagles was mixed with VWF aptamer (control, 6.25 nM, 12.5 nM, 25 nM, and 100 nM), and platelet reactivity was assessed (Platelet Function Analyser-100). Statistical analysis was performed using a two-way ANOVA with multiple comparisons. Results: Bolus VWF aptamer restored carotid blood flow in male mice (Figure 1), compared to females (p 〈 0.001) and vehicle (p 〈 0.01). With continuous infusion, reperfusion in female mice was significantly higher than vehicle (p 〈 0.01). Male canines (264.3 ± 70.3 s) demonstrated significantly more platelet inhibition (p 〈 0.01) than females (175.3 ± 83.2 s) at the 12.5 nM VWF aptamer concentration. Conclusions: Following VWF inhibition, in vivo thrombolytic efficacy in mice is gender dependent, while ex vivo platelet activity varies in canines. The mechanisms underlying these differences in platelet biology are unclear, but this indicates that the VWF-GP IB-IX-V axis plays a role.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.37.suppl_1.143
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
1494427-3
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